Studies are in progress for purification of granulocyte colony stimulating factor (CSF) which is obtained from the growth of L-cells in culture. Steps include adsorption and elution from calcium phosphate gel, anion exchange chromatography, Sephadex gel filtration and adsorption and elution from Con-A-Sepharose. Once sufficiently pure material has been obtained, studies will be conducted to determine the biologic activity of this material in experimental animals. In order to determine the relative importance of serum CSF and high molecular weight lipoprotein inhibitors in the recovery from granulopoiesis, animals are rendered neutropenic and the serum activities of these factors determined. Lipoprotein inhibitors are separated from sera by column chromatographic techniques and assayed in serial dilutions in order to measure quantitative changes in inhibitor levels. Animals will be examined both during the neutropenic and neutrophilic rebound following the administration of cytotoxic agents. A variety of patients with neutropenia and unexplained neutrophilia will be evaluated for granulocyte stem cell content and serum and urine colony stimulating factor activity. Moreover, patients with drug-induced agranulocytosis will be evaluated by in vitro culture technique to determine the mechanism of drug interaction with their marrow stem cells. BIBLIOGRAPHIC REFERENCES: Zidar, B.L., Mendelow, H., Winkelstein, A., and Shadduck, R.K. Diphenylhydantoin induced serum sickness with fibrin-platelet thrombi in lymph node microvasculature. Am. J. Med. 58:704-708, 1975. Shadduck, R.K., and Metcalf, D. Preparation and neutralization characteristics of an anti-CSF antibody. J. Cell. Physiol. 86:247-252, 1975.